Is germline genome-editing person-affecting or identity-affecting, and does it matter?

Writers have debated whether germline genome-editing is person-affecting or identity-affecting. The difference is thought to be ethically relevant to whether we should choose genome-editing or choose preimplantation genetic diagnosis and embryo selection, when seeking to prevent or produce bad conditions (e.g.

Longitudinal imaging of the taste bud in vivo with two-photon laser scanning microscopy.

Taste bud cells in the tongue transduce taste information from chemicals in food and transmit this information to gustatory neurons in the geniculate ganglion that innervate taste buds. The peripheral taste system is a dynamic environment where taste bud cells are continuously replaced, but further understanding of this phenomenon has been limited by the inability to directly observe this process. To overcome this challenge, we combined chronic in vivo two-photon laser scanning microscopy with genetic labeling of gustatory neurons and taste buds to observe how cells within the taste bud change over time.

Protocol for Xenium spatial transcriptomics studies using fixed frozen mouse brain sections.

Here, we present a protocol for Xenium spatial transcriptomics studies using fixed frozen mouse brain sections. We describe steps for intracardiac perfusion, cryosectioning, and floating section mounting of brain sections, which enable runs on the Xenium analyzer and data delivery. We demonstrate that, in addition to the 10× Genomics-validated formalin-fixed paraffin-embedded (FFPE) and fresh frozen sections, fixed frozen thin brain sections are compatible with the Xenium platform and provide excellent imaging and quantification results for spatially resolved gene expression.

A type VI secretion system in species and triggers distinct macrophage death pathways independent of the pyrin inflammasome.

The complex contains opportunistic pathogens that cause chronic infections and inflammation in the lungs of people with cystic fibrosis. Two closely related species within this complex are and the recently classified and encode a type VI secretion system and the effector TecA, which is detected by the pyrin/caspase-1 inflammasome, and triggers macrophage inflammatory death. We previously showed that the pyrin inflammasome was dispensable for lung inflammation in mice infected with AU1054 indicating this species activates an alternative pathway of macrophage inflammatory death.

The impact of determinants of health on the relationship between stigma and health in people living with HIV.

Determinants of health are important drivers of health states, yet there is little work examining their role in the relationship between HIV stigma and health. This study uses moderation analysis to examine how determinants of health affect the relationship between enacted, internalized, and anticipated stigma and mental health. Quantitative data was collected on 337 participants in Ontario, Canada at baseline (t) between August 2018 and September 2019 and at follow-up (t) between February 2021 and October 2021.

TGFβ primes alveolar-like macrophages to induce type I IFN following TLR2 activation.

Alveolar macrophages (AMs) are key mediators of lung function and are potential targets for therapies during respiratory infections. TGFβ is an important regulator of AM differentiation and maintenance, but how TGFβ directly modulates the innate immune responses of AMs remains unclear. This shortcoming prevents effective targeting of AMs to improve lung function in health and disease.

Microglia are dispensable for experience-dependent refinement of mouse visual circuitry.

To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits.

A Type VI Secretion System in Species and Triggers Distinct Macrophage Death Pathways Independent of the Pyrin Inflammasome.

The complex contains opportunistic pathogens that cause chronic infections and inflammation in lungs of people with cystic fibrosis. Two closely related species within this complex are and the recently classified and encode a type VI secretion system and the effector TecA, which is detected by the pyrin/caspase-1 inflammasome, and triggers macrophage inflammatory death. In our earlier study the pyrin inflammasome was dispensable for lung inflammation in mice infected with AU1054, indicating this species activates an alternative pathway of macrophage inflammatory death.

Be a Champion! An Approach to Medical Emergency Response In Situ Simulations in the Outpatient Setting.

Results from a needs assessment conducted by nursing professional development practitioners across several clinics in the Midwest showed current educational methods to prepare for medical emergencies were insufficient. A champion model was used to complete in situ medical emergency response simulations. This proved to be an effective method for staff preparation when resources were limited and identified opportunities for practice improvement.

Evaluation of a pharmacist-led workflow for the FDA Expanded Access Program.

Purpose: This project aimed to characterize the resources necessary for pharmacists to support the required steps for obtaining and handling investigational drugs outside of a study protocol in the individual patient and intermediate-size population Expanded Access Program (EAP) processes. The second aim was to characterize the types of EAP requests received.

Summary: This retrospective, single-center, observational study was performed by reviewing EAP requests initiated at Duke University Hospital (DUH) between August 1, 2017, and February 11, 2023.

Spine surgeon triage of new patient referrals: quantification of surgical conversion rate by clinic referral source.

Background Context: In an effort to efficiently deliver high-value spine surgical care, spine surgery clinics may triage new patient referrals. A triage system with attending surgeon review of referred patient images may improve the surgical conversion rate (SCR) of a spine surgical clinic, and shift the distribution of new patients in clinic toward those most likely to derive benefit from surgery.

Purpose: To quantify SCR and number of triage steps by referral source in a tertiary referral spine clinic where all referrals are triaged by attending surgeons.

Modular vector assembly enables rapid assessment of emerging CRISPR technologies.

The diversity of CRISPR systems, coupled with scientific ingenuity, has led to an explosion of applications; however, to test newly described innovations in their model systems, researchers typically embark on cumbersome, one-off cloning projects to generate custom reagents that are optimized for their biological questions. Here, we leverage Golden Gate cloning to create the Fragmid toolkit, a modular set of CRISPR cassettes and delivery technologies, along with a web portal, resulting in a combinatorial platform that enables scalable vector assembly within days. We further demonstrate that multiple CRISPR technologies can be assessed in parallel in a pooled screening format using this resource, enabling the rapid optimization of both novel technologies and cellular models.

Meaningful inclusion of people living with HIV as a model for workplace policies: Key findings from the project PEER study.

Background: As a large number of people live with HIV, it is worthwhile to examine the integration of this group in the workplace.

Objective: To investigate how the operationalization of GIPA/MEPA supports workplace policies and practices for PLHIV. The study aims to explore what is being offered to support PLHIV in community-based agencies and what can be done to enhance the offerings.

Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes.

Objectives: Glycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D.

Methods: Glomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.

What Do Patients Encounter When Searching Online About Meniscal Surgery? An Analysis of Internet Trends.

Background: Many patients use the internet to learn about their orthopaedic conditions and find answers to their common questions. However, the sources and quality of information available to patients regarding meniscal surgery have not been fully evaluated.

Purpose: To determine the most frequently searched questions associated with meniscal surgery based on question type and topic, as well as to assess the website source type and quality.

Factors Influencing PROMIS Scores and Patient Reported Outcomes Following Surgical Intervention of Isolated Lisfranc Injury: Minimum 2 Year Follow-up.

Lisfranc injuries are rare but significant foot injuries, as they often result from polytrauma patients, and are often misdiagnosed, which further complicate their evaluation and contribute to their propensity towards disability. It is recommended that, on diagnosis, Lisfranc injuries be treated as soon as possible to decrease the risk of future chronic pain, disability, or osteoarthritis. Our study evaluated patients who completed the patient reported outcome measurement information systems (PROMIS) along with the foot function index (FFI) following operative fixation for Lisfranc injury.